The overall goals of the Vermont SCOR are: to gain more precise understanding of lung cell function and cell and tissue pathology as related to specific etiologic agents of pulmonary fibrosis; and hence to improve the diagnosis and treatment of fibrotic lung disease. The program utilizes human specimens, animal models and in vitro cell systems to investigate and compare the responses of human and animal lung macrophages and fibroblasts to known and suspected fibrogenic substances, principally, silica, kaolinite and acrolein. There are studies of the physicochemical characterization of the etiologic agent, deposition and clearance, biochemical, metabolic and cytokinetic characteristics of cellular responses, the organization of such responses as tissue fibrosis, and the expression of such tissue processes as the development of abnormal morphology, physiology, biochemistry and clinical facets of organ disease collectively known as pulmonary fibrosis. The SCOR supplemental application is composed of 3 separate projects. Each is designed to take advantage of recent findings made by our SCOR in the past one and one-half years and/or to expand our approach in specific critical areas of our research program. A more complete biochemical characterization of lavage samples of normal volunteers and fibrosis patients will be undertaken by Project 10. Studies will be expanded to examine the biology and response to fibrogenic agents of human epithelial cells (Project llS) recovered by lavage from patients with fibrotic lung disease and normal volunteers. Finally, efforts will be made to characterize the mechanopharmacology of and the distribution of contractile proteins in normal and fibrotic peripheral lung (Project 13).